CN115887293A - Temperature and light dual-response type slow-release bacteriostatic gel, preparation method and application - Google Patents
Temperature and light dual-response type slow-release bacteriostatic gel, preparation method and application Download PDFInfo
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- CN115887293A CN115887293A CN202211311881.XA CN202211311881A CN115887293A CN 115887293 A CN115887293 A CN 115887293A CN 202211311881 A CN202211311881 A CN 202211311881A CN 115887293 A CN115887293 A CN 115887293A
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- solution
- chitosan
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- release
- stirring
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- 229940005550 sodium alginate Drugs 0.000 claims abstract description 27
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 claims abstract description 26
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Classifications
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
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- Medicinal Preparation (AREA)
Abstract
The invention particularly relates to a temperature and light dual-response type slow-release antibacterial gel, a preparation method and application thereof, wherein the antibacterial gel comprises the following components: the composition comprises octoxyglycan microcapsules, triethanolamine, methyl hydroxybenzoate, polyelectrolyte aqueous solution, carbomer sodium, hydroxypropyl methylcellulose, a buffer solution and a solvent. The octaphenyl polysaccharide microcapsule comprises a mixed core material and a composite wall material, wherein the mixed core material is octaphenyl polyether-10, octaphenyl polyether-30 and octaphenyl polyether-33, and the composite wall material is a modified chitosan, sodium alginate and ethyl cellulose composite wall material; the mass percentage ratio of the mixed core material to the composite wall material is 1: (2-3); the modified chitosan is chitosan which is subjected to quaternization modification and poly-N-isopropylacrylamide modification in sequence. The gel has excellent bacteriostatic effect, and improves the slow release effect and application effectiveness of the gel by combining the slow release microcapsule with temperature and light dual responses.
Description
Technical Field
The invention belongs to the technical field of antibacterial materials, and particularly relates to temperature and light dual-response type sustained-release antibacterial gel, and a preparation method and application thereof.
Background
Disinfection and sterilization are very important parts of life. In daily life, people often use hand-washing disinfection products to keep clean, the frequency and the requirements of hand-washing solutions and disinfection gels are continuously improved, and the effects of disinfection, sterilization, no-washing and the like are gradually increased from washing, so that the hand-washing solutions with various effects are continuously brought out, and the no-washing disinfectant also gradually enters the visual field. When a wound occurs, the requirements of people on disinfection and sterilization are further improved, the wound is the injury of the superficial dermis and the epidermal layer caused by multiple factors, and the wound is difficult to heal because inflammation reaction and bacterial infection often occur. Antibiotics are the most widely used antibacterial drugs at present, but the use is not standard and drug resistance is easy to generate, and inorganic antibacterial agents such as metal oxides of silver, zinc, copper, titanium and the like and ions thereof have broad-spectrum antibacterial activity, but the potential toxicity and the biological safety of the inorganic antibacterial agents are still needed to be further researched. The gel has the effects of lubricating skin and protecting wound surfaces, and can increase the local accumulation effect of the medicine on the skin to achieve sustained release, so that the preparation of the gel with bacteriostasis and healing promotion on the wound surfaces from the perspective of biological materials is very significant.
Patent CN114191620A discloses a hydrogel coating, a supported antibacterial coating, and preparation methods and applications thereof. The hydrogel coating is obtained by in-situ polymerization crosslinking of a raw material containing a zwitterionic monomer and a chemical crosslinking agent on the surface of a polymer matrix. The functional groups containing positive and negative charges uniformly distributed on the zwitter-ion monomer in the hydrogel coating are easy to combine with water molecules, can be used as a barrier for reducing the attachment of protein and bacteria and inhibiting the initial adhesion of the bacteria, and the hydrogel coating is crosslinked in situ on the substrate and is not easy to fall off, so that the replacement frequency of an implanted device can be reduced, and the pain and the medical cost are reduced. Meanwhile, the hydrogel coating is used as a carrier, and the antibacterial agent can be loaded through various non-covalent actions, so that the antibacterial property of the coating is improved. However, the gel of the invention has no slow release function, and the stability of the medicine is poor.
Patent CN112107593A discloses a washing-free hand-protecting bacteriostatic gel and a preparation method thereof, belonging to the technical field of antibacterial disinfection. The washing-free hand-protecting bacteriostatic gel comprises the following components: 0.01-0.5% of hydrolyzed sodium hyaluronate, 0.01-5% of cutin care agent, 0.1-0.5% of thickening agent, 1-10% of emollient, 0.1-0.5% of pH regulator, 56-75% of ethanol and the balance of water; the hydrolyzed sodium hyaluronate is one or more of 500-20000 daltons in average molecular weight, and optionally contains 0-0.5% of macromolecular sodium hyaluronate by mass ratio. The washing-free hand-protecting bacteriostatic gel has the advantages of sterilization, moisture preservation, hand protection, washing-free and the like, and particularly when butanediol and glycerol are simultaneously used as emollients, the bacteriostatic efficiency of a product can reach more than 99% when the ethanol content is only 68%, and the bacteriostatic ability of the product is basically equal to that of a product with the ethanol content of 75%. However, the invention has more ethanol, many people are allergic to ethanol, and the invention has more side effects, which limits the application and popularization of the invention.
Therefore, in order to improve the efficacy and application of the gel, intelligent drugs become a new research direction. The intelligent medicine is a drug delivery system with a self-feedback function, which is formed by an intelligent high-molecular carrier, the intelligence is mainly expressed on the intelligent high-molecular carrier, and the intelligent high-molecular carrier material is a new material which can coordinate various functions in the material through the system, is sensible and responsive to the environment and has function discovery capability. The most widely studied intelligent polymer materials are environment-responsive polymer gels, which can effectively respond to surrounding environmental stimuli such as temperature, pH, ions, electric fields, magnetic fields, solvents, reactants, light or stress and the like, and change their properties, i.e., undergo expansion and contraction, which can reach tens of times or even thousands of times. Because of the unique responsiveness of the environment-responsive polymer gel, the polymer gel has good application prospects in the aspects of chemistry and chemical engineering, biomedicine, drug carriers and the like.
Patent CN109820854a discloses a supramolecular photoresponse drug, and a preparation method and a regulation and control method thereof. The invention provides an active compound modified by an azobenzene group, wherein the azobenzene group is connected with an active substance through a covalent bond; the supramolecular photoresponse drug is assembled with cyclodextrin through the action of a supramolecular host and an object to obtain the supramolecular photoresponse drug. The invention also provides a method for regulating and controlling the antibacterial activity of the supramolecular photoresponse medicine, and the antibacterial activity of the supramolecular photoresponse medicine is improved by ultraviolet irradiation; and, inhibiting its antibacterial activity by visible or non-visible light. The regulation and control method has a wider antibacterial regulation and control range, can be used as a means for effectively controlling the drug resistance of antibiotics, and has a good clinical application prospect. Although the used antibiotics are the most widely applied antibacterial drugs at present, the photoresponse drug has poor stability, is not used in a standard way, and easily causes a large number of drug-resistant bacteria to appear due to abuse of the antibiotics, so that the photoresponse drug can not be used in daily life.
Patent CN110066309A discloses a thermo-sensitive-photosensitive dual stimulus responsive supramolecular organic gel. The invention relates to a gelator containing azobenzene group, the chemical formula of which is C 156 H 240 N 8 O 18 . The supramolecular organogel prepared by the gelator has the characteristics of temperature-sensitive and photosensitive dual response, and is particularly characterized in that the supramolecular organogel can generate gel-sol phase transformation after being heated to 80 ℃, and gradually recovers the gel state after standing at room temperature. Under the irradiation of ultraviolet light with the wavelength of 365nm, gel-sol phase transformation occurs, and the gel state can be slowly recovered after the irradiation of visible light with the wavelength of 450 nm. The supermolecule organogel has good temperature-sensitive-photosensitive performance, and can be used as a temperature-sensitive-photosensitive intelligent gel material to be applied to the fields of sensors, intelligent switches, ion detectors and the like. However, the invention can not meet higher requirements of bacteriostasis and the like.
Patent CN113069545A discloses a long-acting antibacterial material with underwater adhesion photo-thermal dual responsiveness, and preparation and application thereof. According to the invention, 11-mercaptoundecanoic acid is adopted to carry out sulfhydrylation modification on hydroxypropyl cellulose, and then a nanogold rod is grafted on the cellulose by utilizing the strong bonding force of a sulfur-gold bond, so that the long-acting antibacterial material with underwater adhesion photo-thermal dual responsiveness is obtained. The long-acting antibacterial material with underwater adhesion photo-thermal dual responsiveness has good adhesion, can still keep higher viscosity in water, can meet the antibacterial effect of cow mastitis, can enhance the antibacterial effect and the adhesion by grafting the nano gold rod, and is more favorable for preventing and treating the cow mastitis. Although the invention adopts the photothermal dual-response antibacterial material, the material has no slow-release effect and short onset time, and cannot meet the clinical use requirement.
Therefore, how to obtain a high-efficiency antibacterial gel with slow release performance, strong stability and intelligent response to light and temperature becomes a technical problem to be solved in the field.
Disclosure of Invention
Aiming at the defects in the prior art, the invention aims to provide the slow-release antibacterial gel which has double response to temperature and light, slow-release performance and good bactericidal effect, the preparation method thereof and the application thereof in the field of antibacterial materials.
Specifically, the invention provides a temperature and light dual-response type slow-release bacteriostatic gel which comprises the following components in parts by weight:
the octylbenzene polysaccharide microcapsule comprises a mixed core material and a composite wall material, wherein the mixed core material is octylphenol polyether-10, octylphenol polyether-30 and octylphenol polyether-33, and the composite wall material is a modified chitosan, sodium alginate and ethyl cellulose composite wall material;
the mass percentage ratio of the mixed core material to the composite wall material is 1: (2-3);
the modified chitosan is chitosan which is subjected to quaternization modification and poly-N, N-diethylacrylamide modification in sequence.
The octoxynol is a natural active microecological preparation, can cause the content of cells to leak out by destroying cell membranes of bacteria and envelope substances of viruses, provides other components to enter the cells to further play a role in killing, kills 6 kinds of 20 pathogens and male sperms, protects reproductive organs from being invaded by various bacteria, viruses, fungi, chlamydia, mycoplasma and trichomonas, is safe, nontoxic and can be used for a long time.
Triethanolamine is used as pH regulator to regulate pH value of the antibacterial gel to 5.0-5.8.
The methylparaben is also called methylparaben, is mainly used as a sterilization preservative for organic synthesis, foods, cosmetics and medicines, and the mutual matching of the octoxynol, the triethanolamine and the methyl hydroxybenzoate can play a role in synergy and effectively inhibit pathogens.
The carbomer sodium and the polyelectrolyte aqueous solution can form a cross-linked framework, so that active ingredients in the gel can stay in a body for a long time, a drug slow-release medium is provided, the time for the drug to be exerted is prolonged, and the local drug concentration is prevented from being too high.
Further, the polyelectrolyte aqueous solution is at least one of sodium alginate solution, chitosan solution, carrageenan solution and oxidized starch solution.
Further, the buffer solution is a buffer pair solution consisting of sodium dihydrogen phosphate and disodium hydrogen phosphate with the volume percentage of 1 (0.8-1.2), and the solvent is glycerol.
Further, the preparation method of the octoxysan microcapsule comprises the following steps:
step 1: preparing modified chitosan;
step 2: dispersing sodium alginate in distilled water, dispersing modified chitosan in acetic acid solution, heating to dissolve, and swelling for 8-12h;
and step 3: adding the modified chitosan solution into the sodium alginate solution, and stirring to obtain a base material solution;
and 4, step 4: mixing the mixed core material and ethyl cellulose, adding dichloromethane to obtain a mixed solution, dripping the mixed solution into the base material liquid while stirring, and stirring for 5-8 hours after dripping is finished;
and 5: introducing nitrogen, adding the poly-N, N-diethyl acrylamide polymer and the azobisisobutyronitrile, and reacting for 4-8h;
and 6: and centrifuging to collect microcapsule particles, repeatedly cleaning, and drying to obtain the octoxynol microcapsule.
The octoxynol microcapsule has an excellent slow release function by adopting a quaternized chitosan, sodium alginate and ethyl cellulose composite wall material.
Alginic acid is a natural polymer existing in brown algae, sodium alginate is easily combined with some divalent cations to form gel, and the sodium alginate is suitable to be used as microcapsules for embedding medicaments, proteins and cells due to the mild sol-gel process and good biocompatibility. Sodium alginate as natural polyanion compound has a great amount of carboxyl groups on its molecular chain, and can form microcapsules with positively charged high molecular compounds such as chitosan, polylysine and polyarginine by an interfacial polymerization method under the action of static electricity.
Chitosan is also called chitosan, is the only basic polysaccharide in natural polysaccharide, and has the characteristics of wide source, no toxicity, easy chemical modification, biocompatibility, good adsorbability, film forming property, biodegradability and the like. Due to the superior functional properties and the unique molecular structure, the chitosan is used as a biodegradable material for a novel drug delivery system, can greatly improve the curative effect of the drug by changing the drug delivery route, and has the effects of controlling release, increasing targeting property, reducing stimulation and toxic and side effects, improving the passage of hydrophobic drugs through cell membranes, increasing the stability of the drug and the like.
Two active reactive groups are distributed on the macromolecular chain of chitosan, free amino groups in weak acid solution can combine with protons to form polyelectrolyte with positive charge, and the polyelectrolyte has strong adsorption and chelating capabilities, can be used as an immobilized carrier of cells and biomacromolecules, and is easy to chemically modify. The N-acetamido, hydroxyl and amino form various intramolecular and intermolecular hydrogen bonds, and the chitosan molecules are easier to form a crystallization area due to the existence of the hydrogen bonds, so that the chitosan has higher crystallinity and has good physical and mechanical properties such as adsorbability, film forming property, fiber forming property, moisture retention and the like. The chitosan can be used for preparing various microcapsules or microspheres with the functions of loading, targeting, controlled release and the like, such as chitosan porous microspheres, chitosan nanospheres and chitosan-sodium alginate microcapsules.
Because of the water insolubility, the ethyl cellulose is mainly used as a tablet adhesive, a film coating material and the like, and can also be used as an encapsulating auxiliary material to prepare a slow-release microcapsule, so that the drug effect is continuously released, and the premature action of some water-soluble drugs is avoided.
Therefore, the composite wall material prepared from the sodium alginate, the chitosan and the ethyl cellulose can improve the slow release function and the stability of the microcapsule.
The microcapsule has photosensitivity, responsiveness is realized by utilizing ionization effect generated by light decomposition of photosensitive molecules, a large amount of ions are generated in gel after illumination, so that the concentration difference of the ions inside and outside the gel is changed, the osmotic pressure inside the gel is mutated, a solvent is diffused from outside to inside, the gel is promoted to generate volume phase transformation, and a medicament is released. The temperature and light dual-response type microcapsule prepared by the invention overcomes the influence of temperature diffusion on the response speed of single temperature-responsive hydrogel, can generate instantaneous response to light by utilizing the light-responsive hydrogel, and improves the stability and the slow-release function of the gel.
Furthermore, the mass ratio of the octyl phenol polyether-10, the octyl phenol polyether-30 and the octyl phenol polyether-33 in the mixed core material is 1 (2-4) to (0.5-1), and the mass ratio of the modified chitosan, the sodium alginate and the ethyl cellulose in the composite wall material is 2 (1-3) to (1-3).
Further, the preparation method of the modified chitosan specifically comprises the following steps:
s1: dispersing chitosan in water, dropwise adding glacial acetic acid, and stirring;
s2: adding glycidol trimethyl ammonium chloride, and stirring at 50-65 ℃ to obtain a quaternized chitosan solution;
s3: dissolving poly-N-isopropyl acrylamide and N, N-methylene bisacrylamide in deionized water to obtain a photosensitive solution;
s4: adding the photosensitive solution into the quaternized chitosan solution, uniformly mixing, and introducing N 2 Reacting for 20-30min to obtain a mixed solution;
s5: and adding the mixed solution into an acetone solution, stirring, filtering, repeatedly rinsing the obtained solid with ethanol, and drying to obtain the modified chitosan.
The chitosan is subjected to quaternization modification and poly-N-isopropyl acrylamide modification twice in sequence, firstly, the quaternization modified chitosan maintains the characteristic that quaternary ammonium salt is easy to dissolve in water, and simultaneously enhances the antibacterial performance of both the quaternary ammonium salt and the chitosan, so that the water solubility of the quaternization chitosan is enhanced, and meanwhile, the performances of antibiosis, moisture preservation, hemostasis, film formation and the like can be improved. In addition, the skin is the largest organ of the human body, and the stratum corneum in the epidermis is the main barrier for transdermal drug delivery, so that the preparation of nanoparticles of smaller particle size to penetrate the barrier is a major problem. The nanoparticles prepared from chitosan can control the particle size of the nanoparticles, and can be small enough to penetrate through the horny layer and enter the dermis layer to play the role of the medicament, so that the problem of medicament limitation is solved.
Secondly, the chitosan modified by poly-N-isopropylacrylamide has temperature sensitivity, so that the antibacterial hydrogel prepared by the invention has the characteristic of high-temperature shrinkage gel, and particularly, under the condition of low temperature, the hydrogen bond acting force between hydrophilic groups and water molecules in the polymer is very strong, so that the polymer molecules are in a good hydration state in water and fully extend to form a net structure, and further, water and medicaments are dispersed in the polymer network structure to be in a swelling state. And when the temperature is increased, the hydrogen bonding force between hydrophilic groups and water molecules in the polymer is weakened, and the interaction force of hydrophobic groups is strengthened, so that the gel network is shrunk, and water or the medicine in the gel is released.
Further, the mass ratio of chitosan to glycidol trimethyl ammonium chloride is 1: (1.2-1.5), wherein the mass ratio of the poly-N-isopropylacrylamide to the N, N' -methylenebisacrylamide is 1: (0.02-0.2).
Further, the pH value of the slow-release antibacterial gel is 5.0-5.8.
In a second aspect, a preparation method of the temperature-light dual-response type slow-release bacteriostatic gel is provided, which comprises the following steps:
(1) Preparing octoxynol microcapsules;
(2) Mixing the octoxysan microcapsules, benzalkonium chloride and a polyelectrolyte aqueous solution, and stirring to obtain a mixture A;
(3) Mixing carbomer sodium, methyl hydroxybenzoate and triethanolamine, and stirring to obtain a mixture B;
(4) And adding the mixture A, the mixture B, the buffer solution and the hydroxypropyl methyl cellulose into the solvent, and stirring to obtain the slow-release antibacterial gel.
In a third aspect, an application of the temperature-light dual-response type slow-release bacteriostatic gel in the field of bacteriostatic materials is provided.
The invention has the advantages that:
1) The antibacterial gel provided by the invention can play a role in synergistic effect by the mutual matching of the specific components and the dosage of the octoxynol, the triethanolamine and the methylparaben, effectively inhibits pathogens, and has excellent antibacterial performance.
2) The octoxynol microcapsule provided by the invention enables the antibacterial gel to have dual responsiveness to temperature and light and an excellent slow release function. The composite wall material prepared by sodium alginate, chitosan and ethyl cellulose improves the slow release function and stability of the microcapsule. The temperature and light dual-response type microcapsule prepared by the invention overcomes the influence of temperature diffusion on the response speed of single temperature-response hydrogel, and utilizes the light-response hydrogel to generate transient response to light, thereby improving the stability and the slow release function of the gel.
3) The chitosan is subjected to quaternization modification and poly-N-isopropyl acrylamide modification twice in sequence, the water solubility of the chitosan subjected to quaternization modification is enhanced, meanwhile, the performances of antibiosis, moisture preservation, hemostasis, film formation and the like can be improved, the quaternization chitosan is used as an immunopotentiator and can promote cellular immunity and humoral immunity, the particle size of nanoparticles prepared from the chitosan can be controlled, and the nanoparticles can be small enough to penetrate through a stratum corneum and enter a dermis layer to play a role of medicines, so that the problem of medicine limitation is solved.
Detailed Description
In order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention will be further described in detail with reference to the following examples.
A temperature and light dual-response type slow-release bacteriostatic gel comprises the following components in parts by weight:
the octylbenzene polysaccharide microcapsule comprises a mixed core material and a composite wall material, wherein the mass percentage ratio of the mixed core material to the composite wall material is 1: (2-3); the mixed core material consists of octyl phenol polyether-10, octyl phenol polyether-30 and octyl phenol polyether-33 in the mass ratio of 1 (2-4) to 0.5-1, and the composite wall material is a modified chitosan, sodium alginate and ethyl cellulose composite wall material in the mass ratio of 2 (1-3) to (1-3).
The polyelectrolyte aqueous solution is at least one of sodium alginate solution, chitosan solution, carrageenan solution and oxidized starch solution. The buffer solution is a buffer pair solution consisting of sodium dihydrogen phosphate and disodium hydrogen phosphate with the volume percentage of 1 (0.8-1.2), and the solvent is glycerol.
The pH value of the slow-release antibacterial gel is 5.0-5.8.
A preparation method of temperature-light dual-response type slow-release bacteriostatic gel comprises the following steps:
(1) Preparing octoxynol microcapsules;
step 1: preparing modified chitosan:
s1: dispersing chitosan in water, dropwise adding glacial acetic acid, and stirring for 10-12h;
s2: adding glycidol trimethyl ammonium chloride, and stirring at 50-65 ℃ for 12-18h to obtain a quaternary ammonification chitosan solution, wherein the mass ratio of chitosan to glycidol trimethyl ammonium chloride is 1: (1.2-1.5);
s3: dissolving poly-N-isopropylacrylamide and N, N '-methylene bisacrylamide in deionized water to obtain a photosensitive solution, wherein the mass ratio of the poly-N-isopropylacrylamide to the N, N' -methylene bisacrylamide is 1: (0.02-0.2);
s4: adding the photosensitive solution into the quaternized chitosan solution, uniformly mixing, and introducing N 2 Reacting for 20-30min to obtain a mixed solution;
s5: adding the mixed solution into an acetone solution, stirring for 3-5h, filtering, repeatedly rinsing the obtained solid with ethanol, and drying the rinsed solid at 50-80 ℃ for 40-48h to obtain the modified chitosan.
And 2, step: dispersing sodium alginate in distilled water, dispersing modified chitosan in 1-3% acetic acid solution, heating at 50-70 deg.C for dissolving, and swelling for 8-12 hr;
and step 3: adding the modified chitosan solution with the mass fraction of 0.1-0.5% into the sodium alginate solution with the mass fraction of 0.2-0.5%, and stirring at the speed of 600-1000rpm for 6-8h to obtain a base material solution;
and 4, step 4: mixing the mixed core material with ethyl cellulose, adding dichloromethane to obtain a mixed solution, dripping the mixed solution into the base material liquid while stirring at the speed of 100-200rpm, and stirring at the speed of 100-200rpm for 5-8h after dripping is finished;
and 5: introducing nitrogen, adding N-isopropyl acrylamide polymer and azodiisobutyronitrile, and reacting for 4-8h;
step 6: and centrifuging to collect microcapsule particles, repeatedly cleaning, and drying to obtain the octoxynol microcapsule.
(2) Mixing the octoxysan microcapsules, benzalkonium chloride and polyelectrolyte aqueous solution, and stirring at the speed of 200-300r/min to obtain a mixture A;
(3) Mixing carbomer sodium, methyl hydroxybenzoate and triethanolamine, and stirring at 500-600r/min to obtain mixture B;
(4) And adding the mixture A, the mixture B, the buffer solution and the hydroxypropyl methyl cellulose into the solvent, and stirring at the speed of 400-500r/min to obtain the slow-release antibacterial gel.
Example 1
A temperature and light dual-response type slow-release bacteriostatic gel comprises the following components in parts by weight:
the octylbenzene polysaccharide microcapsule comprises a mixed core material and a composite wall material, wherein the mass percentage ratio of the mixed core material to the composite wall material is 1:2; the mixed core material comprises octyl phenol polyether-10, octyl phenol polyether-30 and octyl phenol polyether-33 in a mass ratio of 1.
The polyelectrolyte aqueous solution is at least one of sodium alginate solution, chitosan solution, carrageenan solution and oxidized starch solution. The buffer solution is buffer pair solution consisting of sodium dihydrogen phosphate and disodium hydrogen phosphate with the volume percentage of 1:1, and the solvent is glycerol.
The pH of the slow-release bacteriostatic gel is 5.5.
A preparation method of temperature-light dual-response type slow-release bacteriostatic gel comprises the following steps:
(1) Preparing octobenglycan microcapsules;
step 1: preparing modified chitosan:
s1: dispersing chitosan in water, dropwise adding glacial acetic acid, and stirring for 10h;
s2: and (2) adding glycidol trimethyl ammonium chloride, and stirring at 60 ℃ for 16h to obtain a quaternized chitosan solution, wherein the mass ratio of chitosan to glycidol trimethyl ammonium chloride is 1:1.3;
s3: dissolving poly-N-isopropylacrylamide and N, N '-methylene bisacrylamide in deionized water to obtain a photosensitive solution, wherein the mass ratio of the poly-N-isopropylacrylamide to the N, N' -methylene bisacrylamide is 1:0.1;
s4: adding the photosensitive solution into the quaternized chitosan solution, uniformly mixing, and introducing N 2 Reacting for 25min to obtain a mixed solution;
s5: and adding the mixed solution into an acetone solution, stirring for 45h, filtering, repeatedly rinsing the obtained solid with ethanol, and drying the rinsed solid at 60 ℃ for 45h to obtain the modified chitosan.
And 2, step: dispersing sodium alginate in distilled water, dispersing modified chitosan in 2% acetic acid solution, heating at 60 deg.C for dissolving, and swelling for 10 hr;
and step 3: adding a modified chitosan solution with the mass fraction of 0.4% into a sodium alginate solution with the mass fraction of 0.3%, and stirring at the speed of 800rpm for 7 hours to obtain a base material solution;
and 4, step 4: mixing the mixed core material with ethyl cellulose, adding dichloromethane to obtain a mixed solution, dripping the mixed solution into the base material liquid while stirring at the speed of 150rpm, and stirring at the speed of 100rpm for 6 hours after dripping is finished;
and 5: introducing nitrogen, adding N-isopropyl acrylamide polymer and azodiisobutyronitrile, and reacting for 4-8h;
step 6: and centrifuging to collect microcapsule particles, repeatedly cleaning, and drying to obtain the octoxynol microcapsule.
(2) Mixing the octoxynol microcapsules, benzalkonium chloride and a polyelectrolyte aqueous solution, and stirring at the speed of 200r/min to obtain a mixture A;
(3) Mixing carbomer sodium, methyl hydroxybenzoate and triethanolamine, and stirring at a speed of 600r/min to obtain a mixture B;
(4) And adding the mixture A, the mixture B, the buffer solution and the hydroxypropyl methyl cellulose into the solvent, and stirring at the speed of 400r/min to obtain the slow-release antibacterial gel.
Example 2
The present example differs from example 1 in that: the antibacterial gel has different contents of components.
A temperature and light dual-response type slow-release bacteriostatic gel comprises the following components in parts by weight:
example 3
This example differs from example 1 in that: the antibacterial gel has different contents of components.
A temperature and light dual-response type slow-release bacteriostatic gel comprises the following components in parts by weight:
comparative example 1
This comparative example differs from example 1 in that: the content of each component of the antibacterial gel is different, and the antibacterial gel is specifically as follows:
comparative example 2
This comparative example differs from example 1 in that octaphenyl glycan was added alone and was not prepared in the form of microcapsules.
Comparative example 3
This comparative example differs from example 1 in that the chitosan from which the octoxysan microcapsules were prepared was not quaternized with the modification of poly-N-isopropylacrylamide.
Comparative example 4
This comparative example differs from example 1 in the preparation steps of the microcapsules, which are specifically shown below:
(1) Preparing octoxynol microcapsules;
step 1: preparing modified chitosan:
s1: dispersing chitosan in water, dropwise adding glacial acetic acid, and stirring for 10h;
s2: and (2) adding glycidol trimethyl ammonium chloride, and stirring at 60 ℃ for 16h to obtain a quaternized chitosan solution, wherein the mass ratio of chitosan to glycidol trimethyl ammonium chloride is 1:1.3;
s3: dissolving poly-N-isopropylacrylamide and N, N '-methylenebisacrylamide in deionized water to obtain a photosensitive solution, wherein the mass ratio of the poly-N-isopropylacrylamide to the N, N' -methylenebisacrylamide is 1:0.1;
s4: adding the photosensitive solution into the quaternized chitosan solution, uniformly mixing, and introducing N 2 Reacting for 25min to obtain a mixed solution;
s5: and adding the mixed solution into an acetone solution, stirring for 45h, filtering, repeatedly rinsing the obtained solid with ethanol, and drying the rinsed solid at 60 ℃ for 45h to obtain the modified chitosan.
And 2, step: dispersing sodium alginate in distilled water, dispersing modified chitosan in 2% acetic acid solution, heating at 60 deg.C for dissolving, and swelling for 10 hr;
and step 3: adding a modified chitosan solution with the mass fraction of 0.4% into a sodium alginate solution with the mass fraction of 0.3%, and stirring at the speed of 800rpm for 7 hours to obtain a base material solution;
and 4, step 4: mixing the mixed core material with ethyl cellulose, adding dichloromethane to obtain a mixed solution, dripping the mixed solution into the base material liquid while stirring at the speed of 150rpm, and stirring at the speed of 100rpm for 6 hours after dripping is finished;
and 5: and centrifuging to collect microcapsule particles, repeatedly cleaning, and drying to obtain the octoxynol microcapsule.
Performance testing
1. The bacteriostatic gel obtained in example 1 is subjected to strain bacteriostatic rate detection
Test strains: escherichia coli (ATCC 25922), staphylococcus aureus (ATCC 6538) and Candida albicans (ATCC 10231), wherein the generation numbers of the above strains are 3-5, and bacterial suspension is prepared by using a solution containing 0.03 mol/LPBS.
Graduated pipettes (0.1 mL, 1.0mL, 5.0mL, 10.0 mL), and the like.
The detection method comprises the following steps: the test is carried out according to appendix C4 of GB15979-2002 hygienic Standard for Disposable sanitary articles, and the test is repeated for 3 times by using stock solution of antibacterial gel sample with action time of 2min, 5min, 10min and 20min. The test temperature was 24 ℃. The results of the experiment are shown in table 1:
TABLE 1 bacteria inhibition rate test result table
And (4) conclusion: the slow-release bacteriostatic gel has strong bacteriostatic action on escherichia coli, staphylococcus aureus and candida albicans for 2-10min, has the bacteriostatic rate of more than 99.9 percent, and meets the requirement of appendix C4 of GB15979-2002 sanitation Standard for Disposable sanitary articles.
2. The bacteriostatic gels obtained in examples 1-3 and comparative examples 1-4 are subjected to strain bacteriostatic rate detection
Test strains: escherichia coli (ATCC 25922), staphylococcus aureus (ATCC 6538) and Candida albicans (ATCC 10231), wherein the generation numbers of the above strains are 3-5, and bacterial suspension is prepared by using a solution containing 0.03 mol/LPBS.
Graduated pipettes (0.1 mL, 1.0mL, 5.0mL, 10.0 mL), and the like.
The detection method comprises the following steps: the test is carried out according to appendix C4 of GB15979-2002 hygienic Standard for Disposable sanitary articles, and the sample 'gel' stock solution is used for 2min, 5min, 10min and 20min. The test temperature was 24 ℃.
The bacteriostatic rate results are shown in table 2 below:
TABLE 2 bacteriostatic rate test results table
And (4) conclusion: from the experimental results, the slow-release antibacterial gel has good antibacterial effect and slow-release effect, the antibacterial rate is still over 99.9% after the gel is used for 10 minutes, the antibacterial effect of the gel is influenced by changing the parts of the components, and the slow-release function of the gel is poor when the octoxynol microcapsules are added independently.
3. The bacteriostatic gels obtained in examples 1-3 and comparative examples 1-4 are subjected to temperature response detection
3 parts of 15mg octylbenzene polysaccharide microcapsules are weighed out in the dark and added into 5ml PBS buffer solution with the temperature of 20 ℃, 30 ℃ and 40 ℃ respectively, and the slow release is carried out under the pH value of 5 respectively. Taking 3ml of supernatant after 10 hours, measuring the absorbance of the solution, simultaneously adding 3ml of fresh PBS buffer solution with the corresponding temperature, keeping the total volume of the solution constant, and finally calculating the cumulative release rate of the drug, wherein the results are shown in the following table:
note: the drug release rate in this experiment was the maximum drug release rate.
As can be seen from the cumulative release rates of the drugs at different temperatures, the release rate of the drugs is increased along with the increase of the temperature, so that the octoxynol microcapsules have temperature responsiveness.
4. The bacteriostatic gels obtained in examples 1-3 and comparative examples 1-4 are subjected to photoresponse detection
1 part of 15mg of octoxynan microcapsules is weighed into 5ml of PBS buffer solution with the temperature of 37 ℃ and the pH value of 5 respectively under the condition of keeping out of the light and the condition of illumination. Taking 3ml of supernatant after 10 hours, measuring the absorbance of the solution, simultaneously adding 3ml of fresh PBS buffer solution with corresponding temperature and pH value, keeping the total volume of the solution constant, and finally calculating the cumulative release rate of the medicine, wherein the results are shown in the following table:
note: the drug release rate in this experiment was the maximum drug release rate.
As can be seen from the drug cumulative release rate under different illumination conditions, the drug release rate under the illumination conditions is higher, so that the octoxynol microcapsule has photometric responsiveness.
In conclusion, the sustained-release bacteriostatic gel has a strong bacteriostatic effect, has an outstanding sustained-release effect after the octoxynol microcapsules are added, has dual responsiveness to temperature and light, has high stability, and can continuously exert the effect of active ingredients.
The foregoing describes the preferred embodiment of the present invention, and is intended to provide a clear and understandable description of the invention, but not to limit the invention, and all changes, substitutions and modifications made within the spirit and principle of the invention are included in the scope of the invention as outlined by the appended claims.
Claims (10)
1. The temperature and light dual-response type slow-release bacteriostatic gel is characterized by comprising the following components in parts by weight:
the octaphenyl polysaccharide microcapsule comprises a mixed core material and a composite wall material, wherein the mixed core material is octaphenyl polyether-10, octaphenyl polyether-30 and octaphenyl polyether-33, and the composite wall material is a modified chitosan, sodium alginate and ethyl cellulose composite wall material;
the mass percentage ratio of the mixed core material to the composite wall material is 1: (2-3);
the modified chitosan is chitosan which is subjected to quaternization modification and poly-N, N-diethylacrylamide modification in sequence.
2. The slow-release bacteriostatic gel according to claim 1, wherein the polyelectrolyte aqueous solution is at least one of sodium alginate solution, chitosan solution, carrageenan solution and oxidized starch solution.
3. The slow-release bacteriostatic gel according to claim 2, wherein the buffer solution is a buffer pair solution consisting of sodium dihydrogen phosphate and disodium hydrogen phosphate with the volume percentage of 1 (0.8-1.2), and the solvent is glycerol.
4. The slow-release bacteriostatic gel according to claim 1, wherein the preparation method of the octa-benzene glycan microcapsule comprises the following steps:
step 1: preparing modified chitosan;
step 2: dispersing sodium alginate in distilled water, dispersing modified chitosan in acetic acid solution, heating to dissolve, and swelling for 8-12 hr;
and step 3: adding the modified chitosan solution into the sodium alginate solution, and stirring to obtain a base material solution;
and 4, step 4: mixing the mixed core material with ethyl cellulose, adding dichloromethane to obtain a mixed solution, dripping the mixed solution into the base material liquid while stirring, and stirring for 5-8h after dripping is completed;
and 5: introducing nitrogen, adding poly-N, N-diethyl acrylamide polymer and azodiisobutyronitrile, and reacting for 4-8h;
step 6: and (4) centrifuging to collect microcapsule particles, repeatedly cleaning, and drying to obtain the octoxynol microcapsules.
5. The slow-release bacteriostatic gel according to claim 4, wherein the mass ratio of the octyl phenol polyether-10, the octyl phenol polyether-30 and the octyl phenol polyether-33 in the mixed core material is 1 (2-4) to (0.5-1), and the mass ratio of the modified chitosan, the sodium alginate and the ethyl cellulose in the composite wall material is 2 (1-3) to (1-3).
6. The slow-release bacteriostatic gel according to claim 4, wherein the preparation method of the modified chitosan specifically comprises the following steps:
s1: dispersing chitosan in water, dropwise adding glacial acetic acid, and stirring;
s2: adding glycidol trimethyl ammonium chloride, and stirring at 50-65 ℃ to obtain a quaternized chitosan solution;
s3: poly-N-isopropyl acrylamide and N, N ， Dissolving methylene bisacrylamide in deionized water to obtain a photosensitive solution;
s4: adding the photosensitive solution into the quaternized chitosan solution, uniformly mixing, and introducing N 2 Reacting for 20-30min to obtain a mixed solution;
s5: and adding the mixed solution into an acetone solution, stirring, filtering, repeatedly rinsing the obtained solid with ethanol, and drying to obtain the modified chitosan.
7. The slow-release bacteriostatic gel according to claim 6, wherein the mass ratio of the chitosan to the glycidyltrimethylammonium chloride is 1: (1.2-1.5), wherein the mass ratio of the poly-N-isopropylacrylamide to the N, N' -methylenebisacrylamide is 1: (0.02-0.2).
8. The sustained-release bacteriostatic gel of claim 1, wherein the pH of the sustained-release bacteriostatic gel is 5.0-5.8.
9. A method for preparing a temperature-light dual response type slow release bacteriostatic gel according to any one of claims 1 to 8, which comprises the following steps:
(1) Preparing octoxynol microcapsules;
(2) Mixing the octoxysan microcapsules, benzalkonium chloride and a polyelectrolyte aqueous solution, and stirring to obtain a mixture A;
(3) Mixing carbomer sodium, methyl hydroxybenzoate and triethanolamine, and stirring to obtain a mixture B;
(4) And adding the mixture A, the mixture B, the buffer solution and the hydroxypropyl methyl cellulose into the solvent, and stirring to obtain the slow-release antibacterial gel.
10. The application of the temperature-light dual response type slow-release bacteriostatic gel as defined in any one of claims 1-8 in the field of bacteriostatic materials.
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